Brain, Vol 120, Issue 9 1513-1531, Copyright © 1997 by Oxford University Press
CR Slater, C Young, SJ Wood, GS Bewick, LV Anderson, P Baxter, PR Fawcett, M Roberts, L Jacobson, J Kuks, A Vincent and J Newsom-Davis
Congenital myasthenic syndromes are a heterogeneous group of conditions in
which muscle weakness resulting from impaired neuromuscular transmission is
often present from infancy. One form of congenital myasthenic syndrome is
due to a reduction of the number of acetylcholine receptors (AChRs) at the
neuromuscular junction. We describe four new cases of AChR deficiency,
characterized by a reduction in both miniature endplate potential amplitude
and AChR abundance accompanied by elongation of the neuromuscular junction
and some decrease in postsynaptic folding. A number of cytoplasmic proteins
are normally associated with the postsynaptic membrane and may contribute
to the clustering of AChRs at the neuromuscular junction. We therefore
investigated the expression of several of these proteins in these
AChR-deficiency patients. In each patient, immunolabelling of the
neuromuscular junction for rapsyn, dystrophin, beta-dystroglycan and a form
of beta-spectrin was strong but that for utrophin was markedly reduced or
absent. This suggested that a defect in utrophin expression might underlie
the congenital AChR deficiency. However, a reduction in utrophin labelling
was also seen in three patients with adult acquired autoimmune myasthenia
gravis in whom AChR loss results directly from the extracellular binding of
autoantibodies. We conclude that the loss of AChRs in AChR deficiency does
not result from the absence of rapsyn or beta-dystroglycan and that
reduction of utrophin is probably secondary to the loss of AChRs. The
possible role of AChRs and/or utrophin in determining the extent of
postsynaptic folding is discussed.
ARTICLES
Utrophin abundance is reduced at neuromuscular junctions of patients with both inherited and acquired acetylcholine receptor deficiencies
Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle upon Tyne, UK.
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